Lp(a) is an LDL-like lipoprotein which is highly associated with risk of premature atherosclerotic cardiovascular disease. The protein which identifies this unique lipoprotein is apo(a), which has high homology with plasminogen. Apo(a) is polymorphic, with many different sizes of this protein in the population. This size polymorphism is genetically determined, and in turn, is a major determinant of the plasma level of Lp(a). We previously established that in individuals with the same apo(a) isoform but different levels of Lp(a), variation in the production rate of Lp(a) is the cause of the variation in plasma Lp(a) levels. More recently, we have performed a series of kinetic studies in individuals heterozygous for two forms of apo(a) and directly compared the metabolism of both forms in the same individuals. The size of the apo(a) isoform does not affect its catabolic rate, but rather the rate of its production. This establishes the metabolic basis for the association between apo(a) isoform size and plasma Lp(a) level, and directs attention to the mechanism by which the apo(a) size may affect its rate of biosynthesis. There has been controversy about whether the LDL receptor may be responsible for catabolism of Lp(a) in vivo. We investigated this question by studying the catabolism of Lp(a) in three patients with homozygous familial hypercholesterolemia (FH) who lack the LDL receptor. In all three patients, the catabolism of Lp(a) was similar to that in control subjects, indicating that the LDL receptor is not physiologically important for Lp(a) catabolism. Instead, elevated plasma levels of Lp(a) in homozygous FH were shown to be due to increased production of Lp(a). Furthermore, in these studies we demonstrated for the first time that some Lp(a) is converted in vivo to LDL, providing important information about the metabolic pathways of Lp(a). These studies included subjects of age 19 to 74 years. 45% of the subjects were women. The studies included one Asian and two Hispanic subjects.